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    Controversies in anticoagulation therapy in patients with cirrhosis. Sasso Roula,Rockey Don C Current opinion in gastroenterology PURPOSE OF REVIEW:This article aims to review the latest literature on prophylactic and therapeutic anticoagulation and the safety profile of anticoagulants in patients with cirrhosis. RECENT FINDINGS:The understanding of hematological hemostasis is cirrhotic patients has changed drastically in recent years. Although in the past, cirrhotic patients were often considered to be 'auto-anticoagulated' and at higher risk of bleeding, recent studies have demonstrated that there may be a rebalance in procoagulation and anticoagulation factors in patients with cirrhosis. This, and clinical experience, suggest that cirrhotic patients are at risk of development of venous thrombosis, pulmonary embolism and ischemic strokes and as such, the best management approaches in these patients remains controversial. The bulk of the data suggest that patients with cirrhosis who are at risk for thrombotic or embolic complications should be anticoagulated. However, it is imperative that they be closely monitored. SUMMARY:The medical literature on anticoagulation in patients with liver cirrhosis is conflicting and limited to small sample observational studies. However, most studies suggest that in patients with early stages of liver cirrhosis and no history of varices, anticoagulation appears to be well tolerated. 10.1097/MOG.0000000000000523
    Oral Anticoagulation in Patients With Liver Disease. Qamar Arman,Vaduganathan Muthiah,Greenberger Norton J,Giugliano Robert P Journal of the American College of Cardiology Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. 10.1016/j.jacc.2018.03.023
    Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Liver Disease: A Meta-Analysis and Systematic Review. Fu Yonghui,Zhu Wengen,Zhou Yue,Chen He,Yan Lan,He Wenfeng American journal of cardiovascular drugs : drugs, devices, and other interventions BACKGROUND:The effect of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and liver disease remains largely unresolved. Therefore, we performed a meta-analysis to compare the efficacy and safety of NOACs with warfarin in this population. METHODS:We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the comparisons of NOACs with warfarin in patients with AF and liver disease. A random-effects model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS:A total of six studies with 41,954 participants were included in this meta-analysis. In AF patients with liver disease, compared with warfarin use, the use of NOACs was associated with reduced risks of all-cause death (RR 0.78, 95% CI 0.66-0.93), major bleeding (RR 0.68, 95% CI 0.53-0.88), and intracranial hemorrhage (RR 0.49, 95% CI 0.41-0.59), but had comparable risks of stroke or system embolism (RR 0.80, 95% CI 0.57-1.12) and gastrointestinal bleeding (RR 0.90, 95% CI 0.61-1.34). In AF patients with cirrhosis, NOACs significantly reduced the risks of major bleeding (RR 0.53, 95% CI 0.37-0.76), gastrointestinal bleeding (RR 0.57, 95% CI 0.38-0.84), and intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.97) compared with warfarin. CONCLUSIONS:Based on current publications, the use of NOACs is at least non-inferior to warfarin in patients with AF and liver disease. 10.1007/s40256-019-00369-x
    Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Advanced Liver Disease: An Exploratory Meta-Analysis. Violi Francesco,Vestri Annarita,Menichelli Danilo,Di Rocco Arianna,Pastori Daniele,Pignatelli Pasquale Hepatology communications Direct oral anticoagulants (DOACs) have had a positive impact in preventing cardioembolic stroke in patients with atrial fibrillation (AF) who were associated with lower bleeding complications; however, data on subjects with concomitant advanced liver diseases (ALDs) are poor. This meta-analysis evaluates bleeding and thromboembolic complications in patients with coexisting AF and ALD who were treated with DOACs or vitamin K antagonists (VKAs). We performed a meta-analysis of randomized controlled trials and observational studies identified by the PubMed and Embase databases using a combination of the following keywords: "direct oral anticoagulants," "advanced liver disease," "cirrhosis," "bleeds," "stroke." No time restriction was applied to the research. Two physicians reviewed data on outcome measures and assessed the quality rating. The main outcome was major bleeding, and the secondary outcomes were bleedings (all, intracranial, and gastrointestinal) and ischemic strokes. A total of four studies (one prospective, three retrospective) were identified involving 3,483 subjects with AF and ALD; of these, 1,547 were on VKAs and 1,936 on DOACs. Advanced liver disease was defined as liver cirrhosis or fibrosis-4 score >3.25. Compared to VKA use, DOAC use was associated with reduced risk for major bleedings (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.44-0.77;  < 0.001), total bleedings (HR, 0.45; 95% CI, 0.36-0.55;  < 0.05), intracranial hemorrhage (HR, 0.51; 95% CI, 0.32-0.80;  < 0.004), and gastrointestinal bleedings (HR, 0.61; 95% CI, 0.42-0.88;  < 0.008). Efficacy analysis showed no significant difference between VKA- and DOAC-treated patients (HR, 0.83; 95% CI, 0.58-1.15;  = 0.31). In patients with AF and ALD, the safety and efficacy profile of DOACs did not appear to differ from those with AF without ALD. 10.1002/hep4.1513
    Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. De Gottardi Andrea,Trebicka Jonel,Klinger Christoph,Plessier Aurélie,Seijo Susana,Terziroli Benedetta,Magenta Lorenzo,Semela David,Buscarini Elisabetta,Langlet Philippe,Görtzen Jan,Puente Angela,Müllhaupt Beat,Navascuès Carmen,Nery Filipe,Deltenre Pierre,Turon Fanny,Engelmann Cornelius,Arya Rupen,Caca Karel,Peck-Radosavljevic Markus,Leebeek Frank W G,Valla Dominique,Garcia-Pagan Juan Carlos, Liver international : official journal of the International Association for the Study of the Liver BACKGROUND:Direct-acting oral anticoagulants (DOACs) are used in patients with splanchnic vein thrombosis (SVT) and cirrhosis, but evidence for safety and efficacy in this setting is limited. Our aim was to identify indications and reasons for starting or switching to DOACs and to report adverse effects, complications and short-term outcome. METHODS:Data collection including demographic information, laboratory values, treatment and complications through the Vascular Liver Disease Interest Group Consortium. RESULTS:Forty-five centres (90%) of the consortium completed the initial eCRF. We report here a series of 94 patients from 17 centres. Thirty-six patients (38%) had cirrhosis. Child-Pugh score was 6 (range 5-8), and MELD score 10.2 (range 6-19). Indications for anticoagulation were splanchnic vein thrombosis (75%), deep vein thrombosis (5%), atrial fibrillation (14%) and others (6%). DOACs used were rivaroxaban (83%), dabigatran (11%) and apixaban (6%). Patients were followed up for a median duration of 15 months (cirrhotic) and 26.5 months (non-cirrhotic). Adverse events occurred in 17% of patients and included one case of recurrent portal vein thrombosis and five cases of bleeding. Treatment with DOACs was stopped in three cases. The major reasons for choosing DOACs were no need for monitoring or inadequacy of INR to guide anticoagulation in cirrhotic patients. Renal and liver function did not change during treatment. CONCLUSIONS:A consistent number of patients with SVT and/or cirrhosis are currently treated with DOACs, which seem to be effective and safe. These data provide a basis for performing randomized clinical trials of DOACs vs. low molecular weight heparin or vitamin K antagonists. 10.1111/liv.13285
    Safety of direct oral anticoagulants vs warfarin in patients with chronic liver disease and atrial fibrillation. Goriacko Pavel,Veltri Keith T European journal of haematology BACKGROUND:A complication of chronic liver disease (CLD) is the abnormality of coagulation. In clinical practice, this increased risk of bleeding has not been identified as a protective factor against stroke or systemic embolism associated with atrial fibrillation (AF). The objective of this study was to assess the safety of direct oral anticoagulant (DOAC) agents vs warfarin in CLD patients with AF. METHODS:This was a retrospective cohort study of patients with CLD and AF initiated on oral anticoagulants. Rates of all-cause bleeding were compared between warfarin and DOAC agents. Secondary endpoints included rates of major bleeding and other risk factors for bleeding on anticoagulant therapy. RESULTS:The all-cause bleeding rates were similar between the groups, with 8.4% per year in the DOAC (n = 75) group and 8.8% in warfarin (n = 158) group (HR 0.9, 95% CI 0.4-1.8). No significant difference was noted in the rate of major bleeding. In the multivariable model, higher MELD-XI score and previous bleed were risk factors associated with increased bleeding. CONCLUSION:No significant differences in bleeding rates were noted in patients treated with warfarin and DOAC agents. Further studies evaluating DOAC agents are needed to better understand the optimal anticoagulation strategy in setting of CLD. 10.1111/ejh.13045
    Efficacy and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Liver Disease: a Meta-Analysis and Systematic Review. Huang Zhi-Chun,Li Chang-Qing,Liu Xiao-Yu,Cao Zhong-Chao,Jia Hai-Yu,Dong Ying,Liu Tian-Long,Sun Jian-Jun Cardiovascular drugs and therapy BACKGROUND:Liver disease is associated with increased bleeding risk. The efficacy and safety of direct oral anticoagulants (DOACs) is a subject of contention in atrial fibrillation (AF) patients with liver disease. METHODS:Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus warfarin in AF patients with liver disease from January 1980 to April 2020. A meta-analysis was conducted using a random-effects model. RESULTS:Six studies involving 41,859 patients were included. Compared with warfarin, DOACs demonstrated significant reduction in ischemic stroke (HR, 0.68; 95% CI (0.54-0.86)), major bleeding (0.74 (0.59-0.92)), and intracranial hemorrhage (ICH) (0.48 (0.40-0.58)), with no significant effect on gastrointestinal bleeding (P = 0.893) in AF patients with liver disease. Similar results were observed in regular-dose, reduced-dose, and active liver disease subgroups, albeit Asian patients had a slight reduction in major bleeding (P = 0.055). Furthermore, the pooled estimates of individual DOAC subgroups indicated that dabigatran and apixaban led to greater safety in major bleeding (P < 0.001), ICH (P < 0.001), and gastrointestinal bleeding (P < 0.005) in these patients. The same trends were observed in AF patients with cirrhosis. CONCLUSIONS:Our findings suggest that DOACs significantly reduce the risk of ischemic stroke, major bleeding, and ICH, with no significant effect on the risk of gastrointestinal bleeding in AF patients with liver disease compared with warfarin. 10.1007/s10557-020-07065-y
    Anticoagulation Therapy in Patients with Liver Cirrhosis is Associated With an Increased Risk of Variceal Hemorrhage. Sasso Roula,Rockey Don C The American journal of medicine OBJECTIVE:The belief that cirrhotic patients are "auto-anticoagulated" often results in anticoagulation therapy being withheld in these patients. We aimed to understand patterns of use of anticoagulation and to determine the risk of bleeding complications in cirrhotic patients. METHODS:We retrospectively analyzed 320 cirrhotic patients treated with anticoagulation therapy from July 15, 2014 to January 30, 2018. We performed bivariate and multivariate analyses to identify risk factors for clinically relevant bleeding. We conducted a separate analysis using propensity score matching to compare bleeding rates of a noncirrhotic cohort group on anticoagulation to anticoagulated patients with cirrhosis. RESULTS:Nonalcoholic steatohepatitis (47%) was the most common cause of cirrhosis, and 49% were classified as Child-Pugh class B, a mean model for end-stage liver disease score of 14 and Charlson comorbidity index of 7. Anticoagulation was initiated for atrial fibrillation/atrial flutter in 56% of patients; warfarin was used in 57% of patients and concomitant use of antiplatelet therapy in 25%. Bleeding occurred in 18%, with upper gastrointestinal bleeding (53%) being the most common source. In the propensity-matched cohort, bleeding rates were higher in cirrhotics than in control patients who were matched for baseline characteristics. In multivariate analysis of the cirrhotic patients, the presence of esophageal varices was associated with higher odds of clinically relevant bleeding. CONCLUSION:Anticoagulated cirrhotic patients who have esophageal varices are at an increased risk of bleeding. We recommend that patients with cirrhosis and esophageal varices who require anticoagulation have their varices managed carefully prior to initiation of anticoagulation. 10.1016/j.amjmed.2019.01.006
    Dabigatran causing severe acute kidney injury in a patient with liver cirrhosis. Li Xin,Cheung Chi Yuen CEN case reports Anticoagulant-related nephropathy (ARN), a significant but frequently undiagnosed problem in patients receiving anticoagulation, is found to be associated with increased renal morbidity and all-cause mortality. While ARN is mainly associated with warfarin use, recent case reports suggest that it may also occur in patients taking direct oral anticoagulants (DOAC). We report a patient who had a history of alcoholic liver cirrhosis and paroxysmal atrial fibrillation, and received dabigatran 110 mg twice daily for 1 year. He presented with gross hematuria and severe acute kidney injury with an international normalized ratio of 4.09. Dabigatran was stopped and he was put on temporary hemodialysis support. His renal function gradually improved when the hematuria subsided. Renal biopsy later confirmed the presence of red blood cell casts inside the renal tubules with features of IgA nephropathy. Finally, his renal function returned back to baseline level. As DOAC has been increasingly used nowadays for the treatment of various thromboembolic diatheses, regular monitoring of renal function is warranted, especially in patients with underlying glomerular diseases and coagulopathy such as chronic liver diseases. 10.1007/s13730-019-00378-4
    Risks Versus Benefits of Anticoagulation for Atrial Fibrillation in Cirrhotic Patients. Choi Jonggi,Kim Junhwan,Shim Ju Hyun,Kim Minsu,Nam Gi-Byoung Journal of cardiovascular pharmacology BACKGROUND & AIMS:To evaluate the clinical benefits and risks of anticoagulation with warfarin in cirrhotic patients with atrial fibrillation (AF). METHODS:A total of 465 cirrhotic patients diagnosed with nonvalvular AF were retrospectively analyzed. We compared incidences of ischemic stroke and major bleeding events between the 2 groups and examined the factors predicting ischemic stroke or major bleeding events. RESULTS:Of 465 patients with AF, 113 (24.3%) received warfarin. Warfarin users had a lower mean Child-Pugh score (6.1 ± 1.5 vs. 7.6 ± 2.6) and a higher mean CHA2DS2VASc score (2.0 ± 2.5 vs. 1.7 ± 1.3) than nonusers (P's < 0.05). Overall, the incidence of ischemic stroke was low in cirrhotic patients with AF. It was not dependent on the CHA2DS2VASc score (hazard ratio, 1.40; 95% confidence interval, 0.96-2.05; P = 0.081), and was comparable in warfarin users (0.9%/person-year) and nonusers (1.2%/person-year). However, the incidence of major bleeding events was significantly higher in warfarin users (5.9% vs. 2.6%; P < 0.05). A multivariate analysis identified warfarin use (2.60; 95% confidence interval, 1.32-5.12) and Child-Pugh score (1.25; 1.04-1.49) as independently associated with bleeding events in these cirrhotic patients (P's < 0.05). There was no correlation between HAS-BLED score and risk of major bleeding (1.20; 0.95-1.52; P = 0.123). CONCLUSIONS:Anticoagulation with warfarin in cirrhotic patients with AF may not significantly reduce the risk of ischemic stroke, whereas it increases hemorrhagic complications. 10.1097/FJC.0000000000000513
    Mortality and hepatic decompensation in patients with cirrhosis and atrial fibrillation treated with anticoagulation. Serper Marina,Weinberg Ethan M,Cohen Jordana B,Reese Peter P,Taddei Tamar H,Kaplan David E Hepatology (Baltimore, Md.) BACKGROUND & AIMS:Outcomes with anticoagulation are understudied in advanced liver disease. We investigated effects of anticoagulation (AC) with warfarin and DOACs on all-cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation. APPROACH & RESULTS:This was a retrospective longitudinal study using national data of US Veterans with cirrhosis at 128 medical centers including cirrhosis patients with incident atrial fibrillation from January 1 2012 to December 31 , 2017 followed through December 31 , 2018. To assess the effects of AC on outcomes, we applied propensity-score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time-dependent confounding. The final cohort included 2,694 cirrhotic veterans with atrial fibrillation (n=1,694 and n=704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow-up. All-cause mortality was lower with warfarin vs. no AC: (PS-matched: hazard ratio (HR) 0.65, 95% CI: 0.55-0.76; MSM models: HR 0.54, 95% CI 0.40-0.73) and DOACs vs. no AC (PS-matched: HR 0.68, 95% CI: 0.50-0.93; MSM models: HR 0.50, 95% CI 0.31-0.81). In MSM models, warfarin (HR 0.29, 95% CI 0.09-0.90) and DOACs (HR: 0.23, 95% CI 0.07-0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin: (HR: 0.49, 95% CI 0.26-0.94). CONCLUSIONS:Warfarin and DOACs were associated with reduced all-cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations. 10.1002/hep.31264
    Direct oral anticoagulants in patients with liver cirrhosis: A systematic review. Hoolwerf Evert Willian,Kraaijpoel Noémie,Büller Harry Roger,van Es Nick Thrombosis research INTRODUCTION:Anticoagulant treatment in patients with liver cirrhosis is challenging. The aim of this systematic review was to evaluate clinical outcomes of direct oral anticoagulant (DOAC) therapy in cirrhosis patients. MATERIALS AND METHODS:A systematic search was performed in MEDLINE, Embase, and conference proceedings up to November 7th, 2017, for studies that evaluated the efficacy and safety of DOACs in cirrhosis patients with venous thromboembolism (VTE), splanchnic vein thrombosis (SVT), or atrial fibrillation (AF). Two authors independently screened titles, abstracts, and full-text articles, and assessed risk of bias. A meta-analysis could not be performed due to heterogeneity of the included studies. RESULTS:Of the 2927 articles assessed, five retrospective cohort studies were included (n = 239, including 20 patients overlap). All studies had fair methodological quality. Two studies evaluated DOAC treatment only, and three also evaluated vitamin K antagonists (VKAs) or low-molecular-weight heparins (LMWHs). Recurrent VTE (DOAC n = 12, LMWH/VKA n = 8) or ischemic stroke (DOAC n = 37, LMWH/VKA n = 9) occurred in none of the patients. Progression of VTE was 8% with DOACs (n = 12) and 13% with VKAs and LWWH (n = 8). Recurrent SVT occurred in 0 to 4% with DOACs (n = 31). Progression of SVT was 0 to 5% with DOACs (n = 24) and 0 to 47% with VKAs and LMWH (n = 33). Major bleeding risk ranged from 4 to 15% with DOACs (n = 172) and from 7 to 28% with VKAs and LMWH (n = 67). All-cause mortality risk was 6% with DOACs (n = 36). CONCLUSIONS:There is paucity of data on the efficacy and safety of DOACs in patients with cirrhosis. This analysis suggests that DOACs may be effective and safe for treatment of VTE, SVT, and AF in these patients. 10.1016/j.thromres.2018.08.011
    Anticoagulation for Atrial Fibrillation in Cirrhosis of the Liver: Are Low-Dose Non-Vitamin K Oral Anticoagulants a Reasonable Alternative to Warfarin? Gallagher Celine,Sanders Prashanthan,Wong Christopher X Journal of the American Heart Association See Article by Lee et al. 10.1161/JAHA.119.012102
    Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulant and Warfarin in Cirrhotic Patients With Nonvalvular Atrial Fibrillation. Lee Hsin-Fu,Chan Yi-Hsin,Chang Shang-Hung,Tu Hui-Tzu,Chen Shao-Wei,Yeh Yung-Hsin,Wu Lung-Sheng,Kuo Chang-Fu,Kuo Chi-Tai,See Lai-Chu Journal of the American Heart Association Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non-vitamin K antagonist oral anticoagulants ( NOAC s) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score-based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.79]; P=0.0030) and all major bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.74]; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low-dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10-15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low-dose NOAC s may be considered for such patients. 10.1161/JAHA.118.011112
    Incidence of bleeding in patients with atrial fibrillation and advanced liver fibrosis on treatment with vitamin K or non-vitamin K antagonist oral anticoagulants. Pastori Daniele,Lip Gregory Y H,Farcomeni Alessio,Del Sole Francesco,Sciacqua Angela,Perticone Francesco,Marcucci Rossella,Grifoni Elisa,Pignatelli Pasquale,Violi Francesco, International journal of cardiology OBJECTIVES:To investigate the incidence of bleeding events in atrial fibrillation (AF) patients treated with vitamin K (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) screened for the presence of liver fibrosis (LF). BACKGROUND:Previous studies provided conflicting results on bleeding risk in AF patients with liver disease on VKAs, and no data on NOACs in this setting are available. METHODS:Post-hoc analysis of a prospective, observational multicentre study including 2330 AF outpatients treated with VKAs (n = 1297) or NOACs (n = 1033). Liver damage was quantified by the FIB-4 score (>3.25), a validated marker of LF. The primary endpoint was the incidence of any bleeding, according to ISTH classification. RESULTS:A high FIB-4 was present in 129 (5.5%) patients: 77 (5.9%) on VKA and 52 (5.0%) on NOACs (p = 0.344). During follow-up, 357 (15.3%) patients experienced a bleeding: 261 (80 major and 180 minor) with VKAs (7.2%/year), and 96 (40 major and 56 minor) with NOACs (6.4%/year). In VKA-treated patients, but not in those on NOACs, FIB-4 >3.25 was associated with higher major bleeding (14.3% vs. 5.6%, log-rank test p < 0.001). Multivariable Cox regression model showed that FIB-4 was associated with major bleeding only in VKA-treated patients (HR: 3.075, 95% CI 1.626-5.818, p = 0.001). On multivariable analysis, FIB-4 was not significantly associated with CVEs neither in VKA or NOAC-treated patients. CONCLUSION:We found a significant association between LF and major bleedings in AF patients treated with VKA, which was not evident in patients on NOACs. 10.1016/j.ijcard.2018.01.097
    Efficacy and safety of anticoagulation for atrial fibrillation in patients with cirrhosis: A systematic review and meta-analysis. Chokesuwattanaskul Ronpichai,Thongprayoon Charat,Bathini Tarun,Torres-Ortiz Aldo,O'Corragain Oisin A,Watthanasuntorn Kanramon,Lertjitbanjong Ploypin,Sharma Konika,Prechawat Somchai,Ungprasert Patompong,Kröner Paul T,Wijarnpreecha Karn,Cheungpasitporn Wisit Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver OBJECTIVE:The atrial fibrillation-related stroke is clearly prevented by anticoagulation treatment, however, management of anticoagulation for AF in patients with cirrhosis represents a challenge due to bleeding concerns. To address this issue, a systematic review and meta-analysis of the literature was performed. METHODS:A literature search for studies reporting the incidence of AF in patients with cirrhosis was conducted using MEDLINE, EMBASE and Cochrane Database, from inception through July 2018. RESULTS:7 cohort studies including 19,798 patients with AF and cirrhosis were identified. The use of anticoagulation (%) among included studies ranged from 8.3% to 53.9%. Anticoagulation use for AF in patients with cirrhosis was significantly associated with a reduced risk of stroke, with a pooled HR of 0.58 (95%CI: 0.35-0.96). When compared with no anticoagulation, the use of anticoagulation was not significantly associated with a higher risk of bleeding, with a pooled HR of 1.45 (95%CI: 0.96-2.17). Compared to warfarin, the use of direct oral anticoagulants (DOACs) was associated with a lower risk of bleeding among AF patients with cirrhosis. CONCLUSION:Our study demonstrates that anticoagulation use for AF in patients with cirrhosis is associated with a reduced risk of stroke, without increasing significantly the risk of bleeding, when compared to those without anticoagulation. 10.1016/j.dld.2018.12.001
    The safety and efficacy of vitamin K antagonist in patients with atrial fibrillation and liver cirrhosis. Lee Seung-Jun,Uhm Jae-Sun,Kim Jong-Youn,Pak Hui-Nam,Lee Moon-Hyoung,Joung Boyoung International journal of cardiology BACKGROUND:Bleeding is a major concern in treatment of atrial fibrillation (AF) with vitamin K antagonist (VKA). This concern is more emphasized in patients with high bleeding risk such as liver cirrhosis (LC). METHODS AND RESULTS:We retrospectively analyzed incidence of stroke and major bleeding in 321 AF patients with LC, including early [Child-Pugh (CP)-A, n=215] and advanced [CP-B or C, n=106] LC according to VKA prescription. The CHA2DS2-VASc, HAS-BLED and MELD scores were higher in patients with VKA. CP score was positively correlated with HAS-BLED score (rho: 0.602). The incidence of major bleeding was higher in advanced LC than in early LC (14.5%/year vs. 4.9%/year, p<0.001). VKA reduced the risk of ischemic stroke in AF patients with LC, whereas it significantly increased the major bleeding risk. There was no difference in survival free from significant clinical events (SCEs) between the patients with or without VKA (p=0.91). On subgroup analysis, VKA was beneficial in early LC patients, as it decreased stroke without increasing major bleeding risk. However, in advanced LC patients, VKA significantly increased the risk of major bleeding, especially variceal origin, that overwhelms stroke reduction. As a result, VKA treatment reduced the risk of SCEs in early LC patients, whereas it increased the risk of SCEs in advanced LC. CONCLUSIONS:VKA treatment might be beneficial to reduce significant clinical events in the early LC but not in the advanced LC group. However to confirm this hypothesis, a prospective randomized study is needed. 10.1016/j.ijcard.2014.11.183
    Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention? Kuo Ling,Chao Tze-Fan,Liu Chia-Jen,Lin Yenn-Jiang,Chang Shih-Lin,Lo Li-Wei,Hu Yu-Feng,Tuan Ta-Chuan,Liao Jo-Nan,Chung Fa-Po,Chen Tzeng-Ji,Lip Gregory Y H,Chen Shih-Ann Journal of the American Heart Association BACKGROUND:Patients with liver cirrhosis have been excluded from randomized clinical trials of oral anticoagulation therapy for stroke prevention in atrial fibrillation. We hypothesized that patients with liver cirrhosis would have a positive net clinical benefit for oral anticoagulation when used for stroke prevention in atrial fibrillation. METHODS AND RESULTS:This study used the National Health Insurance Research Database in Taiwan. Among 289 559 atrial fibrillation patients aged ≥20 years, there were 10 336 with liver cirrhosis, and 9056 of them having a CHADS-VASc score ≥2 were divided into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin. Patients with liver cirrhosis had a higher risk of ischemic stroke (hazard ratio=1.10, =0.046) and intracranial hemorrhage (hazard ratio=1.20, =0.043) compared with those without. Among patients with liver cirrhosis, patients taking antiplatelet therapy had a similar risk of ischemic stroke (hazard ratio=1.02, 95%CI=0.88-1.18) compared to those without antithrombotic therapies, but the risk was significantly lowered among warfarin users (hazard ratio=0.76, 95%CI=0.58-0.99). For intracranial hemorrhage, there were no significant differences between those untreated and those taking antiplatelet therapy or warfarin. The use of warfarin was associated with a positive net clinical benefit compared with being untreated or receiving only antiplatelet therapy. CONCLUSIONS:For atrial fibrillation patients with liver cirrhosis in the current analysis of an observational study, warfarin use was associated with a lower risk of ischemic stroke and a positive net clinical benefit compared with nontreatment, and thus, thromboprophylaxis should be considered for such patients. 10.1161/JAHA.116.005307